Effect of oral cholecalciferol in a murine model of celiac disease: A dose ranging study

• Published in: The Journal of steroid biochemistry and molecular biology 2022-06, Vol.220, p.106083-106083, Article 106083
• Main Authors: Trasciatti, Silvia, Piras, Francesca, Bonaretti, Silvano, Marini, Sandra, Nencioni, Simona, Biasci, Elena, Egan, Colin Gerard, Nannipieri, Fabrizio
• Format: Article
• Language: English
• Subjects: Animal models; CD3 antigen; Celiac disease; Cholecalciferol; Diabetes mellitus; Diet; Gliadin; Gluten; Immunohistochemistry; Intestine; NOD mice; Olive oil; Oral administration; Pathology; Serum levels; Vitamin D; Vitamin D receptors; Vitamin D3; Zonula occludens-1 protein; Zonulin
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2022.106083

Previous studies have shown a relationship between vitamin D and celiac disease (CD), however little evidence is available examining the direct effects of vitamin D on pathological features of this disease. In this study we evaluated the effect of oral administration of different doses of native vitamin D3 (cholecalciferol) in enteropathic mice. Female non-obese diabetic (NOD)/ShiLt.J mice were fed standard or gluten-free diet and administered gliadin (5 μg/kg) to induce a celiac pathology. Healthy control (gluten-free diet, without gliadin) and control for pathology (standard diet, with gliadin) were administered olive oil. All other experimental groups received gliadin and standard diet plus oral cholecalciferol (5, 10, 20, 50 and 130 μg/kg). Serum levels of 25(OH)D3, calcium and zonulin and expression of vitamin D receptor (VDR), CD3 and zonula occludens-1 (ZO-1) by immunohistochemistry as well as intestinal histological and histomorphometric analyses were undertaken. Although no difference in serum levels of 25(OH)D3, calcium or zonulin was observed in cholecalciferol-treated mice vs. healthy controls, a significant improvement in intestinal mucosa pathological features in mice administered cholecalciferol was observed by histological analysis. Villi length was also significantly increased by cholecalciferol in a dose-dependent manner. Immunohistochemical staining revealed increased expression of CD3 and ZO-1 in celiac mice compared to mice receiving high dose (130 μg/kg) cholecalciferol. These findings show the effect of oral cholecalciferol on signature features of CD in a mouse model of CD. Further dose-ranging studies to investigate the efficacy of cholecalciferol for the treatment of CD are warranted. •Few studies have examined the direct effects of vitamin D on pathological features of celiac disease.•A range of doses of vitamin D (cholecalciferol) in celiac and healthy control mice were evaluated.•Cholecalciferol significantly reduced intestinal mucosal lesions and increased villi length in a dose-dependent manner.•Cholecalciferol increased the expression of the lymphocyte CD3 and zonulin/zonula occludens-1 in the intestinal mucosa.•Additional explorative studies will allow a greater understanding of this complex disease.